Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation.

PURPOSES: Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation. METHODS: Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics. RESULTS: The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h(-1) and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution. CONCLUSIONS: We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.

Adenocarcinoma of the duodenum arising in a tubulo-villous adenoma.

Villous adenoma of the duodenum is rare and has a high prevalence of cancer. We report here an unusual case of a 73-year-old man who presented with a tumour on the second part of the duodenum with moderate dysplasia of a tubulo-villous adenoma at the biopsies. A segmental duodeno-jejunal resection was performed and the resection margins were negative. The final histological analysis was a moderately differentiated invasive duodenal adenocarcinoma (pT3Nx). Management of these tumours is discussed here.